Zupin L, Polesello V, Alberi G, Moratelli G, Crocè S L, Masutti F, Pozzato G, Crovella S, Segat L
Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.
Institute for Maternal and Child Health, IRCCS 'Burlo Garofolo', Trieste, Italy.
Scand J Immunol. 2016 Jul;84(1):61-9. doi: 10.1111/sji.12444.
Hepatitis C is disease that damages the liver, and it is caused by the hepatitis C virus (HCV). The pathology became chronic in about 80% of the cases due to virus persistence in the host organism. The standard of care consists of pegylated interferon plus ribavirin; however, the treatment response is very variable and different host/viral factors may concur in the disease outcome. The mannose-binding protein C (MBL) is a component of the innate immune system, able to recognize HCV and consecutively activating the immune response. MBL is encoded by MBL2 gene, and polymorphisms, two in the promoter region (H/L and X/Y) and three in exon 1 (at codon 52, 54 and 57), have been described as functionally influencing protein expression. In this work, 203 Italian HCV patients and 61 healthy controls were enrolled and genotyped for the five MBL2 polymorphisms mentioned above to investigate their role in HCV infection susceptibility, spontaneous viral clearance and treatment response. MBL2 polymorphisms were not associated with HCV infection susceptibility and with spontaneous viral clearance, while MBL2 O allele, O/O genotype, HYO haplotype and DP combined genotype (all correlated with low or deficient MBL expression) were associated with sustained virological response. Moreover, a meta-analysis to assess the role of MBL2 polymorphisms in HCV infection susceptibility was also performed: YA haplotype could be associated with protection towards HCV infection.
丙型肝炎是一种损害肝脏的疾病，由丙型肝炎病毒（HCV）引起。由于病毒在宿主体内持续存在，约80%的病例会发展为慢性病变。标准治疗方案包括聚乙二醇化干扰素加利巴韦林；然而，治疗反应差异很大，不同的宿主/病毒因素可能共同影响疾病的转归。甘露糖结合蛋白C（MBL）是固有免疫系统的一个组成部分，能够识别HCV并继而激活免疫反应。MBL由MBL2基因编码，其启动子区域存在两种多态性（H/L和X/Y），外显子1存在三种多态性（密码子52、54和57处），这些多态性在功能上影响蛋白质表达。在本研究中，招募了203名意大利HCV患者和61名健康对照，对上述5种MBL2多态性进行基因分型，以研究它们在HCV感染易感性、病毒自发清除和治疗反应中的作用。MBL2多态性与HCV感染易感性及病毒自发清除无关，而MBL2 O等位基因、O/O基因型、HYO单倍型和DP联合基因型（均与MBL低表达或缺陷表达相关）与持续病毒学应答相关。此外，还进行了一项荟萃分析以评估MBL2多态性在HCV感染易感性中的作用：YA单倍型可能与HCV感染的保护作用相关。
